Differential distribution of immunoreactive angiotensin and angiotensin-converting enzyme in rat brain

To help resolve the controversy about the brain renin-angiotensin system, the distribution of immunoreactive angiotensin in the brains of male rats was analyzed using twelve different antibodies to angiotensin II, two of which had previously been reported to stain nerve fibers in the central nervous system. The distribution of angiotensin-converting enzyme immunoreactivity was also examined using an antibody to rabbit lung converting enzyme, and the distribution of this immunoreactivity was compared to that of immunoreactive angiotensin. Weak angiotensin-like immunoreactivity was found in cell bodies of the hypothalamic magnocellular nuclei of colchicine-treated rats and in nerve terminals of the median eminence, neurohypophysis, central nucleus of the amygdala, bed nucleus of the stria terminalis and various other sites in the brain and spinal cord of untreated rats. Staining could be demonstrated with only three antisera. Antigenic specificity was carefully studied in these antisera. Each was similar in that staining could be blocked with angiotensins I, II or III and tetradecapeptide renin substrate, although angiotensins II and III were most potent. Because of the relatively few angiotensin II antisera which could stain brain and because they are blockable with angiotensin I and tetradecapeptide renin substrate, the precise nature of immunoreactive angiotensin remains an open question. Intense converting enzyme-like activity was localized in endothelial cells of capillaries throughout the brain, in the subfornical organ and in the 'brush border' of choroidal epithelial cells in contact with cerebrospinal fluid. No activity was detected in neural tissue other than the subfornical organ and occasional weak activity in some ependymal elements elsewhere. These findings indicate that angiotensin and converting enzyme immunoreactivities are not co-distributed and raises several questions regarding the nature of, and pathway for, formation of immunoreactive angiotensin in the brain.